3a9i

Crystal structure of homocitrate synthase from Thermus thermophilus complexed with Lys

spinqualitylabelsall models 3a9i, resolution 1.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3a9i is a 1 chain structure with sequence from Thermus thermophilus HB27. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.8Å Ligands: CO, LYS Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function HOSA_THET2 Catalyzes the aldol-type condensation of 2-oxoglutarate with acetyl-CoA to yield homocitrate (PubMed:19996101, PubMed:12095615). Carries out the first step of the alpha-aminoadipate (AAA) lysine biosynthesis pathway (PubMed:9868782). To a lesser extent, can also use oxaloacetate in place of 2-oxoglutarate, leading to citrate. Does not display 2-isopropylmalate synthase activity since it cannot use 2-oxoisovalerate (PubMed:12095615). Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed Homocitrate synthase (HCS) catalyzes aldol-type condensation of acetyl coenzyme A (acetyl-CoA) and alpha-ketoglutarate (alpha-KG) to synthesize homocitrate (HC), which is the first and committed step in the lysine biosynthetic pathway through alpha-aminoadipate. As known in most enzymes catalyzing the first reactions in amino acid biosynthetic pathways, HCS is regulated via feedback inhibition by the end product, lysine. Here, we determined the crystal structures of HCS from Thermus thermophilus complexed with alpha-KG, HC, or lysine. In the HC complex, the C1-carboxyl group of HC, which is derived from acetyl-CoA, is hydrogen-bonded with His-292* from another subunit (indicated by the asterisk), indicating direct involvement of this residue in the catalytic mechanism of HCS. The crystal structure of HCS complexed with lysine showed that lysine is bound to the active site with rearrangement of amino acid residues in the substrate-binding site, which accounts for the competitive inhibition by lysine with alpha-KG. Comparison between the structures suggests that His-72, which is conserved in lysine-sensitive HCSs and binds the C5-carboxyl group of alpha-KG, serves as a switch for the conformational change. Replacement of His-72 by leucine made HCS resistant to lysine inhibition, demonstrating the regulatory role of this conserved residue. Mechanism of substrate recognition and insight into feedback inhibition of homocitrate synthase from Thermus thermophilus.,Okada T, Tomita T, Wulandari AP, Kuzuyama T, Nishiyama M J Biol Chem. 2010 Feb 5;285(6):4195-205. Epub 2009 Dec 7. PMID:19996101 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Homocitrate synthase

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